A dynamic COVID-19 immune signature includes associations with poor prognosis

Abstract

Improved understanding and management of COVID-19, a potentially life-threatening disease, could greatly reduce the threat posed by its etiologic agent, SARS-CoV-2. Toward this end, we have identified a core peripheral blood immune signature across 63 hospital-treated patients with COVID-19 who were otherwise highly heterogeneous. The signature includes discrete changes in B and myelomonocytic cell composition, profoundly altered T cell phenotypes, selective cytokine/chemokine upregulation and SARS-CoV-2-specific antibodies. Some signature traits identify links with other settings of immunoprotection and immunopathology; others, including basophil and plasmacytoid dendritic cell depletion, correlate strongly with disease severity; while a third set of traits, including a triad of IP-10, interleukin-10 and interleukin-6, anticipate subsequent clinical progression. Hence, contingent upon independent validation in other COVID-19 cohorts, individual traits within this signature may collectively and individually guide treatment options; offer insights into COVID-19 pathogenesis; and aid early, risk-based patient stratification that is particularly beneficial in phasic diseases such as COVID-19.

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

“…T cell exhaustion or dysfunction has been implicated in SARS-CoV-2 infected adults 24,25,76 . The inhibitory receptor PD-1 is often expressed by exhausted T cells but can also be expressed by All rights reserved.…”

SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

“…In this context, circulating SARS-CoV-2 RNA (RNAemia) has been highlighted as a promising prognostic biomarker in hospitalized COVID-19 patients, as it is associated with disease severity 7 and mortality [8][9][10] , with an estimated prevalence of 10% (95% CI 5-18%, random effects model) 7 . Further, we hypothesized that the acute and profound alterations in the innate and adaptive immune system in COVID-19 patients 3,[11][12][13] , especially in RNAemic patients [14][15][16][17][18] , will be accompanied by marked changes in the circulating proteome and interactome and that the proteome in COVID-19 patients will highlight mechanistically relevant signatures and trajectories, when compared to non-COVID-19 sepsis and healthy controls. Thus far, proteomics studies have focused on the determination of protein biomarkers of COVID-19 severity [19][20][21][22] , but have not assessed the longitudinal relationship between proteomic changes, RNAemia and 28-day mortality.…”

COVID-19 and iron dysregulation: distant sequence similarity between hepcidin and the novel coronavirus spike glycoprotein

“…Foremost among the potential physiological connections related to the present discussion is the so-called 'cytokine storm' mediated by interleukin-6 (IL-6) reported in some COVID-19 patients [70,84,87,138]. This is not, however, restricted to IL-6 and in fact elevated levels of a bundle of pro-inflammatory cytokines has been reported in severe COVID-19 cases [25,26].…”